Persorption of Resistant Starch Granules: Should We Be Worried?

I recently wrote a piece that I thought I would try to publish in one of the main-line nutritional journals on a topic in the field of starch that no one in my field seemed to know anything about when I brought up the subject to them. However, when I cast about looking for a journal that would publish the piece, which was not quite long enough for a mini-review, too long for a brief communication, and certainly was no new research paper in its own right, I found only rigid requirements that would not bend and high publishing fees that I can not afford at the time of writing this piece. Thus, I am instead publishing the piece online for all eyes to see.

Credit must be given to Doctor Ray Peat for first introducing me to the persorption phenomenon, which is really a very old discovery. The term refers to the paracellular transport of solid particulates across the intestinal “barrier” – which, coming from someone with numerous food allergies, is a laughable term in itself – and into the lymphatic and circulatory systems, including our main topic of discussion over these last few posts, the starch granule.

Because the research on starch granules was mostly old, not to mention in German, I believe that it has largely failed to cross the Atlantic and penetrate the consciousness of the larger food science and nutrition communities who have investigated the effects of dietary fibres, such as the various forms of resistant starch, ad nauseum. What little has crossed over has been in the pharmaceutical and medical journals, and so I set out to write a short piece on the matter to apprise my fellow food scientists of the phenomenon. I uncovered enough disturbing effects of persorbed starch granules and solid bodies that make their way into the tissues that this post will not be easily accepted. Let the reader judge for himself.

The paper can be found below the break.

Persorption of “Resistant” Starch: Should We Be Worried?

Moore, S. A.

1006 Lincoln Way, Unit #101, Ames, IA 50011, Phone: (540) 834-8924, E-Mail:shmuelhashual@gmail.com

Introduction

The fact that a portion of starch survives digestion under conditions of in vitro digestion with porcine pancreatic α-amylase as an analogue for the human enzyme was first noted by Englyst and co-workers (1982). This fraction of starch was later found to have physical significance in that it also survives in vivo digestion and thereby “resists” absorption in the small intestine of human ileostomy patients (Englyst and Cummings 1987) and was termed “resistant starch” (RS). In following years, the form, morphology, and chemical characteristics of native and chemically-modified starches that qualify as RS were elaborated.

Because RS has a functional, rather than chemical, definition, a number of different classifications or “types” of RS have been enumerated (Englyst and Hudson 1996). RS Type 1 (RS1) is that which is inaccessible to the peptic enzymes, such as in whole grains or coarse meal; RS Type 2 (RS2) is raw starch granules that resist enzyme hydrolysis based on structural characteristics, although some authors (e.g. Alsaffar 2011) make a distinction between thermally stable granules with elevated amylose contents (i.e. ≥ 50% amylose, RS2a) that survive most cooking processes and those with normal amylose contents, such as starch from raw potato or green banana (RS2b); RS3 is retrograded starch crystallites formed by the reassociation of starch chains disordered during cooking; RS4 covers a number of chemical modifications of starch granules that resist digestive enzymes based on chemical characteristics; finally, RS5 is the helical inclusion complex formed between starch chains and lipids and may be either endogenous in the starch source or produced industrially (Hasjim and others 2010). RS has attracted considerable attention for its potential in diabetic therapy, in weight management, and for improving and modulating the microbial constitution of the intestinal microbiome. These aspects have been recently and thoroughly reviewed elsewhere (Birt and others 2013).

Yet prior to and concurrent with the development of the definition of RS, a different phenomenon relating to ingestion of starch was also investigated. The process by which intact solid microparticles on the order of several micrometers exhibit paracellular translocation across the intestinal epithelium into the portal blood, lymph, and eventually into the urine, organs, and capillaries was first noted by Herbst (1844) in the dog and confirmed by Donders (1851) in the frog and rabbit using starch granules as a solid particle. The phenomenon was thus originally termed the “Herbst effect”. Hirsch (1906) was the first researcher to confirm that this effect is also observed in humans, finding that starch granules were present in the urine of volunteers ingesting raw starches of multiple botanical sources several hours post-prandium. This phenomenon came to be termed “persorption” of the particle to distinguish from absorption of dietary components, such as simple sugars. The effect in man was independently confirmed by Verzàr (1911) after attempting to disprove the earlier observations and was not thoroughly treated until a series of reports by Volkheimer investigated the physiological effects and end destination of many types of persorbed particles, including starch granules (Volkheimer 2001). The mechanism for the translocation of solid particles across the intestinal barrier is a combination of kneading into the mucosa via peristalsis and the compression and suction of villous “pumping” action (Volkheimer 2001). To date, raw starch granules have been found in blood (Volkheimer 1974), urine (Hirch 1906, Verzàr 1911), as embolisms in small arterioles (Volkheimer 1974, Freedman 1991), in cerebrospinal fluid (Volkheimer and others 1962), in mesenteric lymph nodes (Hodges and others 1995, Hazzard and others 1996), in the chyle (Volkheimer 1974), and in the lungs (Lamb and Robert 1972). The presence of starch granules in all of these systems suggests that persorbed particles may enter the circulation via the portal vein or lymphatic system. Freedman (1991) hypothesized that starch granules embolizing arterioles in the brain could result in the death of local neurons. Giltzelmann and Spycher (1993) likewise expressed concern over the use of cornstarch in the treatment of glycogen storage diseases in juveniles (Lee and others 1996), which they considered potentially problematic due to the isolated starch granules being very readily absorbed in their young patients.

While unmodified starch is itself relatively inert, any solid microparticle may elicit an inflammatory, immunological response termed a foreign-body giant cell in which macrophages are recruited and fused around the foreign body. Foreign-body giant cells are observed in lungs, lymph nodes, and peritoneal tissue in which intact starch granules have penetrated (Michowitz, Ilie, and Stavorovsky 1983, Lamb and Robert 1972).

Contemporary investigations of the persorption mechanism have shown that microparticles up to 150 μm are transported across the endothelium, although microparticles from 7 – 70 μm are most readily absorbed (Volkheimer 2001). Notably, many common food starches lie in this optimum size range for persorption (Table 1).

Table 1. Particle size range and distribution of common food starches
Starcha	Particle Size (μm), long axis
Rice	3 – 8, compound
Oat	2 – 15, compound
Maize	5 – 20
High-Amylose Maize	6 – 15
Wheat	<10, 22 – 36, bimodal
Potato	15 – 75
Latex Microspheresb	~2
aJane and others 1994 bMcMinn, Hodges, and Carr 1996

Because the lines of inquiry into starch properties and persorption of solid microparticles have advanced independently, and because previous studies have assumed an effective spherical shape of starch granules for sake of simplicity, no report on the persorption of asymmetric starch granules has yet appeared. This dearth of research becomes much more significant in the context of high-amylose maize starches (RS2a), which present elongated granules formed by the fusion of nascent starch granules in amyloplasts due to amylose-amylose helical interactions and are not fully dispersed in normal cooking conditions due to their elevated conclusion gelatinization temperature above the boiling point of water (Jiang and others 2008, Jiang and others 2010). Whether the persorption rate of these long granules corresponds more closely with that of the shorter or the longer axis (6 - 15 μm) is not known (Jane and others 1994).

No study has appeared differentiating between the susceptibility of the different types of RS to persorption. However, encapsulation, as in food matrices constituting RS1, is no protection against persorption after the motions of chewing and peristalsis; starch granules from corn, rolled oats, and cold cereals, such as muesli, have been observed in the blood of human subjects 30 min after ingestion (Nagele and others 2013).

To date, no survey of the persorption of any non-native starch has been reported in the literature. As such, questions as to the toxic effects or intensity of the foreign-body response to chemically modified starch transported to peripheral tissues via the persorptive mechanism remain unanswered. A strong foreign-body response and inflammation of the peritoneal cavity due to infiltration of the highly-cross linked corn starch used as a lubricant in surgical gloves has been reported in the medical literature (Michowitz, Ilie, and Stavorovsky 1983).

Saturated free fatty acids exert a lipotoxic, apoptotic effect on a number of tissues and cell types in vivo and in culture, including the pancreas (Weinberg 2006), muscle (Artwohl and others 2009), sex organs (Mu and others 2001, Lu and others 2003), heart (Vandervusse and others 1992), vascular endothelium (Artwohl and others 2008), and kidney (Weinberg 2006). The debranched high-amylose maize-palmitic or stearic acid complex described by Hasjim (2010) and termed RS5 shows a coating of crystalline fatty acids on the surface of starch granules (Reed, personal communication); whether these crystalline fatty acids may elicit an inflammatory or foreign-body response in peripheral tissue is not known. Similarly, no report has appeared on the quantity of chemically modified starch granules that appear in bodily fluids compared to native counterparts.

Removal of persorbed starch granules from the tissues in which they come to rest appears to be a time-critical process. The predominant means of removal of persorbed particles is via the veinous blood and urine, up to 90% within the first 4 h after ingestion (Volkheimer 2001). Starch particles that remain are largely those embolized in small arterioles or peripheral organs and may therefore participate in foreign-body giant cell reactions. Because the only modified starch granulatoma reported in the medical literature arise from the cross-linked starch used in gloves (Michowitz, Ilie, and Stovorovsky 1983) and condoms (Saxén, Kassinen, and Saxén 1963), the question of whether other types of chemical modifications influence the residence time of persorbed starch granules in tissues should be investigated.

As the benefits of resistant starches in the management of chronic conditions become more widely known and find increasing use in food products as a dietary fibre supplement, the phenomenon of persorption has been largely neglected. Because the starch science community has not conducted any significant research in this area, leaving the advancement of our knowledge of the mechanisms of persorption to the medical and pharmaceutical industries, the technologies and knowledge of the one field have not crossed over to the other, leaving significant gaps in our knowledge of how resistant starches may behave in the body outside of the confines of the alimentary canal. To summarize, the following areas appear to be most in need of further investigation:

1)      Whether the nature of chemical modifications of starch granules, as in RS4, may result in increased dispersion across the intestinal membrane and deposition in peripheral tissues;

2)      Whether chemical modifications of starch granules may increase residence time of persorbed starch granules in peripheral tissues;

3)      Whether observations that glove starch induces inflammatory giant-cell reactions commute to persorbed “resistant” starch granules;

4)      Whether chemical modifications of RS4 or RS5 may cause local excitation and cytotoxicity by auxiliary mechanisms.

Works Cited

Alsaffar, A. A. Effect of food processing on the resistant starch content of cereals and cereal products – a review. International Journal of Food Science & Technology. 2011, 46, 455 – 462

Artwohl, M.; Lindenmair, A.; Roden, M.; Waldäusl, W. K.; Freudenthaler, A.; Klosner, G.; Ilhan, A.; Luger, A.; Baumgartner-Parzer, S. M. Fatty acids induce apoptosis in human smooth muscle cells depending on chain length, saturation, and duration of exposure. Atherosclerosis. 2009, 202, 2, 351 – 362

Artwohl, M.; Lindenmair, A.; Sexl, V.; Maier, C.; Rainer, G.; Freudenthaler, A.; Huttary, N.; Wolzt, M.; Nowotny, P.; Luger, A.; Baumgartner-Parzer, S. M. Different mechanisms of saturated versus polyunsaturated FFA-induced apoptosis in human endothelial cells. Journal of Lipid Research. 2008 49, 12, 2627 – 2640

Birt, D. F.; Boylston, T.; Hendrich, S.; Jane, J.; Hollis, J.; Li, L.; McClelland, J.; Moore, S. A.; Phillips, G. J.; Rowling, M.; Schalinske, K.; Scott, M. P.; Whitley, E. M. Resistant Starch: Promise for Improving Human Health. Advances in Nutrition. 2013, 4, 587 – 601

Donders, F. C. Untersuchungen über den Übergang fester Moleküle in das Gefäβsystem. Zeitschrift fiir rationelle Medizin. 1851, NF 1, 415 – 427

Englyst, H. N.; Cummings, J. H. Digestion of polysaccharides of potato in the small intestine of man. American Journal of Clinical Nutrition. 1987, 45, 423 – 431

Englyst, H. N.; Hudson, G. J. The classification and measurement of dietary carbohydrates. Food Chemistry. 1996, 57, 1, 15 – 21

Englyst, H. N.; Wiggins, H. S.; Cummings, J. H. Determination of the non-starch polysaccharides in plant foods by gas-liquid chromatography of constituent sugars as alditol acetates. Analyst. 1982, 107, 307 – 318

Freedman, B. L. Persorption of raw starch: a cause of senile dementia? Medical Hypotheses. 1991, 5, 2, 85 – 87

Gitzelmann, R.; Spycher, M. A. Oral cornstarch therapy: Is persorption harmless? European Journal of Pediatrics. 1993, 152, 7, 592 – 594

Hasjim, J.; Lee, S.-O.; Hendrich, S.; Setiawan, S.; Ai, Y.; Jane, J. Characterization of a Novel Resistant-Starch and Its Effects on Postprandial Plasma-Glucose and Insulin Responses. Cereal Chemsitry. 2010, 87, 4, 257 – 262

Hazzard, R. A.; Hodges, G. M.; Scott, J. D.; McGuinness, C. B.; Carr, K. E. Early intestinal microparticle uptake in the rat. Journal of Anatomy. 1996, 189, 265 – 271

Herbst, G. Das Lymphgefäβsystem und seine Verrichtung. Vandenhoek & Ruprecht Göttingen. 1844, 333 – 337

Hirsch, R. Über das Vorkommen von Stärkekörnern im Blut und im Urin. Zeitschrift für experimentelle Pathologie und Therapie. 1906, 3, 390

Hodges, G. M.; Carr, E. A.; Hazzard, R. A.; Carr, K. E. Uptake and translocation of microparticles in small intestine. Morphology and quantification of particle distribution. Digestive Diseases and Sciences. 1995, 40, 5, 967 – 975

Hodges, G. M.; Carr, E. A.; Hazzard, R. A.; O’Reilly, C.; Carr, K. E. A commentary on morphological and quantitative aspects of microparticle translocation across the gastrointestinal mucosa. Journal of Drug Targeting. 1995, 3, 1, 57 – 60

Jane, J.; Kasemsuwan, T.; Leas, S.; Zobel, H.; Robyt, J. F. Anthology of Starch Granule Morphology by Scanning Electron Microscopy. Starch/Stärke. 1994, 48, 4, S121 – S129

Jiang, H.; Horner, H. T.; Pepper, T. M.; Blanco, M.; Campbell, Jane, J. Formation of elongated starch granules in high-amylose maize. Carbohydrate Polymers. 2010, 80, 533 – 538

Lamb, D.; Roberts, G. Starch and talc emboli in drug addicts’ lungs. Journal of Clinical Pathology. 1972, 25, 876 – 881

Lee, P. J.; Dixon, M. A.; Leonard, J. V. Uncooked cornstarch – efficacy in type I glycogenosis. Archives of Disease in Childhood. 1996, 74, 546 – 547

Lu, Z. H.; Mu, Y. M.; Wang, B. A.; Li, X. L.; Lu, J. M.; Li, J. Y.; Pan, C. Y.; Yanase, T.; Nawata, H. Saturated free fatty acids, palmitic acid and stearic acid, induce apoptosis by stimulation of ceramide generation in rat testicular Leydig cell. Biochemistry and Biophysics Research Communication. 2003, 303, 4, 1002 – 1007

McMinn, L. H.; Hodges, G. M.; Carr, K. E. Gastrointestinal uptake and translocation of microparticles in the streptozotocin-diabetic rat. Journal of Anatomy. 1996, 189, 553 – 559

Michowitz, M.; Ilie, B.; Stavorovsky, M. Granulomatous peritonitis caused by glove starch. Postgraduate Medical Journal. 1983, 59, 593 – 595

Mu, Y. M.; Yanase, T.; Nishi, Y.; Tanaka, A.; Saito, M.; Jin, C. H.; Mukasa, C.; Okabe, T.; Nomura, M.; Goto, K.; Nawata, H. Saturated FFAs, palmitic acid and stearic acid, induce apoptosis in human granulosa cells. Endocrinology. 2001, 142, 8, 3590 – 3597

Nagele, W.; Müller, N.; Brugger-Pichler, E.; Nagele, J. Persorption Of Plant Microparticles After Oral Plant Food Intake. The Internet Journal of Herbal and Plant Medicine. 2013, 2, 1

Reed, M. Beech Nut Nutrition, Amsterdam, NY. Personal Communication, February 2014.

Saxén, L.; Kassinen, A.; Saxén, E. Peritoneal Foreign-Body Reaction Caused by Condom Emulsion. The Lancet. 1963, 281, 7294, 1295 – 1296

Vandervusse, G. J.; Glatz, J. F. C.; Stam, H. C. G.; Reneman, R. S. Fatty-acid homeostasis in the normoxic and ischemic heart. Physiology Reviews. 1992, 72, 881 – 940

Verzàr, F. Aufsaugung und Ausscheidung von Stärkekörnern. Biochemische Zeitschrift. 1911, 34, 68

Volkheimer, G. [Persorption of microparticles]. Pathologe. 1993, 5, 247 – 252

Volkheimer, G. “The Phenomenon of Persorption: Persorption, Dissemination, and Elimination of Microparticles”. In Old Herborn University Seminar Monograph 14: Intestinal Translocation; Heidt, P. J.; Nieuwenhuis, P.; Rusch, V. D.; van der Waaij, D., Eds.; Herborn Litterae; Herborn-Dill, 2001; pp 7 – 18

Volkheimer, G. Passage of Particles through the Wall of the Gastrointestinal Tract. Environmental Health Perspectives. 1974, 9, 215 – 225

Volkheimer, G.; Schulz, F. H. Persorption of vegetable food particles. Qualitas Plantarum et Materiae Vegetabiles. 1968, 17, 1, 17 – 30

Volkheimer, G.; Schulz, F. H.; Lehmann, H.; Aurich, I.; Hübner, R.; Hübner, M.; Hallmayer, A.; Münch, H.; Oppermann, H.; Strauch, S. Primary portal transport of persorbed starch granules from the intestinal wall. Medicina experimentalis. International Journal of Experimental Medicine. 1968, 18, 2, 103 – 108

Volkheimer, G.; Ulbricht, W.; Al Abesie, F.; John, H.; Wachtel, S. Beobachtungen zur Resorption korpuskulärer Elemente aus dem Darm und deren Vorkommen im Bereich des ZNS und im Liquor cerebrospinalis. Psychiatrie, Neurologie, und medizinische Psychologie. 1962, 14, 129 – 130

Weinberg, J. M. Lipotoxicity. Kidney International. 2006, 70, 1560 – 1566